Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B-cell Responses to Influenza Hemagglutinin

Understanding human vaccine-induced memory B cell responses is critical to developing effective vaccines to evolving viruses like Influenza A. B cell responses to influenza exposure involve activation of pre-existing immunity and generation of new responses. To characterize these two types of responses, we analyzed the response to H7N9 vaccination in H7N9 naïve adults. This allowed us to distinguish responses of pre-existing B cells towards conserved epitopes versus newly generated H7-specific epitopes using hemagglutinin (HA) probes by flow cytometry. The recall response to conserved epitopes on H7 HA involved a transient expansion of memory B cells with little observed adaptation. However, the B cell response to newly encountered epitopes was phenotypically distinct and generated a sustained memory population that evolved and affinity matured months after vaccination. These findings establish clear differences between newly generated and pre-existing memory B cells, highlighting the challenges in achieving long-lasting, broad protection against an ever-evolving virus. Overall design: 34 Samples